ICR5 Antibody

Definition and Target of CCR5 Antibodies

CCR5 (CC chemokine receptor 5) is a G-protein-coupled receptor expressed on immune cells (e.g., CD4+ T cells, macrophages) and plays a critical role in immune responses and inflammatory signaling . CCR5 Antibodies are therapeutic or research tools designed to bind and modulate the receptor, primarily to block viral entry (e.g., HIV) or modulate immune responses .

Key Features of CCR5 Antibodies

Mechanisms of Action

CCR5 Antibodies exert effects through distinct mechanisms depending on their epitope specificity and binding characteristics:

HIV Entry Blockade

CCR5 serves as a co-receptor for HIV-1 entry. Antibodies targeting the N-terminus or ECL2 regions (e.g., Maraviroc-like ligands) block viral gp120 binding . Conversely, antibodies targeting ECL1 (e.g., natural anti-CCR5 Abs in long-term nonprogressors) induce prolonged receptor internalization, preventing HIV infection .

Receptor Occupancy and Immunomodulation

Therapeutic antibodies like Leronlimab (PRO-140) stabilize CCR5 on the cell surface, increasing circulating CCR5+CD4+ T cells while blocking viral entry . This dual mechanism contrasts with small-molecule CCR5 inhibitors, which downregulate surface receptors .

Antibody Specificity and Validation

Early studies highlighted challenges in commercial antibody specificity for CCR5. For example:

• MAB182 (R&D Systems): Validated for flow cytometry and immunofluorescence, detects CCR5 in PBMCs and dendritic cells .

• Leronlimab: Demonstrated 100% receptor occupancy in human peripheral blood CD4+ T cells at 700 mg doses, correlating with plasma viremia suppression .

Clinical and Preclinical Data

Example 1: Leronlimab in HIV Treatment

• Macaque Studies: Weekly 700 mg Leronlimab achieved full CCR5 occupancy, increased CCR5+CD4+ T cells, and suppressed SIV plasma viremia .

• Human Trials: 700 mg doses led to complete CCR5 occupancy and a 2.5-fold increase in peripheral blood CCR5+CD4+ T cells .

Example 2: Natural Anti-CCR5 Antibodies in Long-Term Nonprogressors (LTNPs)

• Prevalence: 23.5% of LTNPs had anti-ECL1 antibodies, which induced stable CCR5 internalization .

• Clinical Impact: Loss of these antibodies correlated with HIV progression .

Cross-Reactivity and Non-Specific Binding

Early commercial antibodies (e.g., ab2932, ab33478) showed poor specificity, detecting non-CCR5 bands in immunoblots . Rigorous validation (e.g., siRNA knockdown, knockout models) remains critical .

Receptor Occupancy Measurement

Traditional flow cytometry methods overestimated CCR5 occupancy due to background noise. Novel methods using Leronlimab-PB (phosphatidylcholine-conjugated Leronlimab) improved sensitivity .

Future Directions

• Therapeutic Optimization: Combining CCR5 antibodies with antiviral drugs for HIV treatment .

• Biomarker Development: Monitoring CCR5+CD4+ T cell levels as a proxy for antibody efficacy .